Atomic structure of the KEOPS complex: an ancient protein kinase-containing molecular machine.
Kae1 is a universally conserved ATPase and part of the essential gene set in bacteria. In archaea and eukaryotes, Kae1 is embedded within the protein kinase-containing KEOPS complex. Mutation of KEOPS subunits in yeast leads to striking telomere and transcription defects, but the exact biochemical function of KEOPS is not known. As a first step to elucidating its function, we solved the atomic structure of archaea-derived KEOPS complexes involving Kae1, Bud32, Pcc1, and Cgi121 subunits. Our studies suggest that Kae1 is regulated at two levels by the primordial protein kinase Bud32, which is itself regulated by Cgi121. Moreover, Pcc1 appears to function as a dimerization module, perhaps suggesting that KEOPS may be a processive molecular machine. Lastly, as Bud32 lacks the conventional substrate-recognition infrastructure of eukaryotic protein kinases including an activation segment, Bud32 may provide a glimpse of the evolutionary history of the protein kinase family.
Mao
Daniel Y L
DY
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada.
Neculai
Dante
D
Downey
Michael
M
Orlicky
Stephen
S
Haffani
Yosr Z
YZ
Ceccarelli
Derek F
DF
Ho
Jenny S L
JS
Szilard
Rachel K
RK
Zhang
Wei
W
Ho
Cynthia S
CS
Wan
Leo
L
Fares
Christophe
C
Rumpel
Sigrun
S
Kurinov
Igor
I
Arrowsmith
Cheryl H
CH
Durocher
Daniel
D
Sicheri
Frank
F
D019843:Archaeal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D017017:Methanococcus / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000502:physiology; D019906:Nuclear Magnetic Resonance, Biomolecular; D011494:Protein Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D016615:Telomere / Q000378:metabolism; D013822:Thermoplasma / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D019843:Archaeal Proteins; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; D021122:Protein Subunits; C533091:TPRKB protein, human; D011494:Protein Kinases